Department of Medicine Faculty PapersCopyright (c) 2015 Thomas Jefferson University All rights reserved.http://jdc.jefferson.edu/medfp
Recent documents in Department of Medicine Faculty Papersen-usTue, 17 Feb 2015 01:34:51 PST3600GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors.http://jdc.jefferson.edu/medfp/121
http://jdc.jefferson.edu/medfp/121Sun, 15 Feb 2015 13:46:45 PST
GATA3 is a transcription factor important in the differentiation of breast epithelia, urothelia, and subsets of T lymphocytes. It has been suggested to be useful in the evaluation of carcinomas of mammary or urothelial origin or metastatic carcinomas, but its distribution in normal and neoplastic tissues is incompletely mapped. In this study, we examined normal developing and adult tissues and 2040 epithelial and 460 mesenchymal or neuroectodermal neoplasms for GATA3 expression to explore its diagnostic value in surgical pathology, using monoclonal antibody (clone L50-823) and Leica Bond automated immunohistochemistry. GATA3 was expressed in trophoblast, fetal and adult epidermis, adult mammary and some salivary gland and sweat gland ductal epithelia, urothelia, distal nephron in developing and adult tissues, some prostatic basal cells, and subsets of T lymphocytes. It was expressed stronger in fetal than in adult mesothelia and was absent in respiratory and gastrointestinal epithelia. In epithelial neoplasms, GATA3 was expressed in >90% of primary and metastatic ductal and lobular carcinomas of the breast, urothelial, and cutaneous basal cell carcinomas and trophoblastic and endodermal sinus tumors. In metastatic breast carcinomas, it was more sensitive than GCDFP. Among squamous cell carcinomas, the expression was highest in the skin (81%) and lower in cervical (33%), laryngeal (16%), and pulmonary tumors (12%). Common positivity was found in skin adnexal tumors (100%), mesothelioma (58%), salivary gland (43%), and pancreatic (37%) ductal carcinomas, whereas frequency of expression in adenocarcinomas of lung, stomach, colon, endometrium, ovary, and prostate was
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Markku Miettinen et al.BiopsyCarcinomaEmbryo, MammalianFemaleGATA3 Transcription FactorGestational AgeHumansImmunohistochemistryMaleNeoplasms, Connective TissueNeuroectodermal TumorsPredictive Value of TestsPrognosisTumor Markers, BiologicalUnderstanding the power of perinatal events and metabolic status in childhood.http://jdc.jefferson.edu/medfp/120
http://jdc.jefferson.edu/medfp/120Fri, 09 Jan 2015 16:49:46 PSTBonita Falkner et al.Birth WeightBlood PressureFemaleHumansMaleMetabolomicsWeight GainBlau Syndrome, the prototypic auto-inflammatory granulomatous disease.http://jdc.jefferson.edu/medfp/119
http://jdc.jefferson.edu/medfp/119Sun, 23 Nov 2014 13:41:20 PST
Blau syndrome is a monogenic disease resulting from mutations in the pattern recognition receptor NOD2, and is phenotypically characterized by the triad of granulomatous polyarthritis, dermatitis and uveitis. This paper reviews briefly the classical clinical features of the disease, as well as more recently described extra-triad symptoms. From an ongoing prospective multicenter study, we provide new data on the natural history of Blau syndrome, focusing on functional status and visual outcome. We also present an update of the range of different NOD2 mutations found in Blau syndrome as well as recent data on morphologic and immunohistochemical characteristics of the Blau granuloma. Finally, emerging insights into pathogenic mechanisms including activation of NOD2 signal transduction, and potential biomarkers of disease activity are discussed.
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Carine H Wouters et al.The new oral anticoagulants for the treatment of venous thromboembolism: a new paradigm shift in antithrombotic therapy.http://jdc.jefferson.edu/medfp/118
http://jdc.jefferson.edu/medfp/118Sun, 16 Nov 2014 17:44:00 PST
BACKGROUND: Several novel oral anticoagulants have been studied for the prevention and treatment of venous thromboembolism (VTE) in different patient populations. Clinicians will increasingly encounter scenarios in which they must choose among these and conventional anticoagulants for the treatment of this potentially fatal condition.

OBJECTIVE: To review the results of Phase III clinical trials that investigated the novel oral anticoagulants for the treatment of deep vein thrombosis and pulmonary embolism. Potential advantages and disadvantages of these anticoagulant agents with respect to each other and conventional therapy will also be explored through a case-based approach.

METHODS: A literature search in PubMed was conducted that identified Phase III clinical trials investigating the novel oral anticoagulant agents for the treatment of VTE.

RESULTS: The new oral anticoagulant agents have been shown to be as safe and effective for the treatment of VTE as conventional therapies.

CONCLUSIONS: These novel, oral anticoagulant agents are legitimate options for the treatment of VTE. A careful assessment of a patient׳s comorbidities, medication use, and laboratory results should be undertaken before prescribing the new oral anticoagulant agents for patients with VTE.

OBJECTIVE: The current study attempted to identify the adiponectin receptor subtype responsible for adiponectin's vascular protective action and investigate the role of ceramidase activation in adiponectin anti-inflammatory signaling.

CONCLUSIONS: These results demonstrate for the first time that adiponectin inhibits TNFα-induced inflammatory response via Cav1-mediated ceramidase recruitment and activation in an AdipoR1-dependent fashion.

Holter monitors are often used for evaluation of palpitations, syncope, heart rate, and detection of arrhythmias

The duration of a typical Holter recording is either 24 or 48 hours

Little research has been targeted at determining the ideal duration of monitoring

We examined the yield of 24 versus 48 hours of Holter monitoring

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Amanda Trang, MD et al.Molecular and functional identification of a mitochondrial ryanodine receptor in neurons.http://jdc.jefferson.edu/medfp/115
http://jdc.jefferson.edu/medfp/115Mon, 14 Jul 2014 11:57:29 PDT
Mitochondrial Ca(2+) controls numerous cell functions, such as energy metabolism, reactive oxygen species generation, spatiotemporal dynamics of Ca(2+) signaling, cell growth and death in various cell types including neurons. Mitochondrial Ca(2+) accumulation is mainly mediated by the mitochondrial Ca(2+) uniporter (MCU), but recent reports also indicate that mitochondrial Ca(2+)-influx mechanisms are regulated not only by MCU, but also by multiple channels/transporters. We previously reported that ryanodine receptor (RyR), which is a one of the main Ca(2+)-release channels at endoplasmic/sarcoplasmic reticulum (SR/ER) in excitable cells, is expressed at the mitochondrial inner membrane (IMM) and serves as a part of the Ca(2+) uptake mechanism in cardiomyocytes. Although RyR is also expressed in neuronal cells and works as a Ca(2+)-release channel at ER, it has not been well investigated whether neuronal mitochondria possess RyR and, if so, whether this mitochondrial RyR has physiological functions in neuronal cells. Here we show that neuronal mitochondria express RyR at IMM and accumulate Ca(2+) through this channel in response to cytosolic Ca(2+) elevation, which is similar to what we observed in another excitable cell-type, cardiomyocytes. In addition, the RyR blockers dantrolene or ryanodine significantly inhibits mitochondrial Ca(2+) uptake in permeabilized striatal neurons. Taken together, we identify RyR as an additional mitochondrial Ca(2+) uptake mechanism in response to the elevation of [Ca(2+)]c in neurons, suggesting that this channel may play a critical role in mitochondrial Ca(2+)-mediated functions such as energy metabolism.
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Regina Jakob et al.Implementation of a Residency Twitter Account to Provide Curricular Enrichmenthttp://jdc.jefferson.edu/medfp/114
http://jdc.jefferson.edu/medfp/114Tue, 08 Apr 2014 10:36:16 PDTBackground

The Problem

With the goals of improving patient safety and resident well-being, the ACGME’s 2011 revision of duty-hour requirements included a 16-hour limit on continuous duty hours for postgraduate year 1 (PGY-1) trainees, increased supervision for junior trainees, as well as mandated rest periods between duty hours.1 These rules place limitations on the ability of trainees to attend scheduled educational activities during standard work hours; a recent study showed a decrease in resident availability for teaching conferences compared with the 2003 duty hour regulations.2 Residency training programs must develop alternative avenues for education and encouraging inquiry outside of traditional methods.

A Modern Solution

Social networking sites, such as Twitter, represent a promising opportunity for residency programs to foster collaborative learning and educational engagement both inside and outside of the hospital. After surveying our residents’ methods of obtaining medical knowledge, the chief medical residents at Thomas Jefferson University Hospital created a shared Twitter account entitled “@JeffIMChiefs” with the goals of disseminating clinical pearls from our daily conferences and inspiring continued learning by providing links to relevant research and review articles.

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Bryan Lebude, MD et al.Comparison Study of Airway Reactivity Outcomes due to a Pharmacologic Challenge Test: Impulse Oscillometry versus Least Mean Squared Analysis Techniques.http://jdc.jefferson.edu/medfp/113
http://jdc.jefferson.edu/medfp/113Wed, 05 Feb 2014 10:22:19 PST
The technique of measuring transpulmonary pressure and respiratory airflow with manometry and pneumotachography using the least mean squared analysis (LMS) has been used broadly in both preclinical and clinical settings for the evaluation of neonatal respiratory function during tidal volume breathing for lung tissue and airway frictional mechanical properties measurements. Whereas the technique of measuring respiratory function using the impulse oscillation technique (IOS) involves the assessment of the relationship between pressure and flow using an impulse signal with a range of frequencies, requires less cooperation and provides more information on total respiratory system resistance (chest wall, lung tissue, and airways). The present study represents a preclinical animal study to determine whether these respiratory function techniques (LMS and IOS) are comparable in detecting changes in respiratory resistance derived from a direct pharmacological challenge.
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Elena Rodriguez et al.Long-term persistency and costs associated with the use of iron chelation therapies in the treatment of Sickle cell disease within Medicaid programs.http://jdc.jefferson.edu/medfp/112
http://jdc.jefferson.edu/medfp/112Wed, 05 Feb 2014 10:11:37 PST
OBJECTIVE: This retrospective study evaluated iron chelating therapy (ICT) discontinuation and costs in Sickle cell disease (SCD) Medicaid recipients using healthcare claims from 2006-2010.

RESULTS: The average age among 404 SCD patients meeting study inclusion criteria was 18.7 (±11.0) years, with 45.8% being males and 66.7% being Blacks. Switches or combinations from DFO at index occurred in 124 (74.7%) patients compared to 10 (4.2%) with DFX at index. The Cox regression model that assessed long-term medication persistence indicated a 1.30-times higher likelihood of treatment discontinuation with DFO compared to DFX (95% CI: 1.06-1.61). Some 19.7% of patient remained on DFX relative to 4.8% on DFO. Both inpatient and total costs were similar in DFX and DFO treatment groups. Following 1 year of treatment, 37.4% remained on DFX compared to 15.7% on DFO. Meaningful differences in treatment discontinuation between the two treatment groups did not occur until 220+ days during the study period. At 18-months, treatment discontinuation rates were high in both groups; 95% for DFO and 80% for DFX.

CONCLUSION: This study of SCD Medicaid patients found more therapeutic switches from DFO to DFX and a higher medication persistency rate with DFX than DFO. The conclusions are limited by the study's retrospective nature, which depends on multivariate statistics to account for patient heterogeneity and risk factors.

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Edward P Armstrong et al.AdolescentAdultAge FactorsAnemia, Sickle CellBenzoatesBlood TransfusionChildContinental Population GroupsDeferoxamineDrug UtilizationFemaleHealth ExpendituresHumansInsurance Claim ReviewIron Chelating AgentsKaplan-Meier EstimateMaleMedicaidMedication AdherencePatient PreferenceProportional Hazards ModelsRetrospective StudiesSex FactorsTriazolesUnited StatesSmooth muscle fascicular reorientation is required for esophageal morphogenesis and dependent on Cdo.http://jdc.jefferson.edu/medfp/111
http://jdc.jefferson.edu/medfp/111Sun, 08 Dec 2013 13:14:49 PST
Postnatal maturation of esophageal musculature involves proximal-to-distal replacement of smooth muscle with skeletal muscle by elusive mechanisms. We report that this process is impaired in mice lacking the cell surface receptor Cdo and identify the underlying developmental mechanism. A myogenic transition zone containing proliferative skeletal muscle precursor cells migrated in a proximal-distal direction, leaving differentiated myofibers in its wake. Distal to the transition zone, smooth muscle fascicles underwent a morphogenetic process whereby they changed their orientation relative to each other and to the lumen. Consequently, a path was cleared for the transition zone, and smooth muscle ultimately occupied only the distal-most esophagus; there was no loss of smooth muscle. Cdo(-/-) mice were specifically defective in fascicular reorientation, resulting in an aberrantly proximal skeletal-smooth muscle boundary. Furthermore, Cdo(-/-) mice displayed megaesophagus and achalasia, and their lower esophageal sphincter was resistant to nitric oxide-induced relaxation, suggesting a developmental linkage between patterning and sphincter function. Collectively, these results illuminate mechanisms of esophageal morphogenesis and motility disorders.
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Anthony I Romer et al.AgingAnimalsCell Adhesion MoleculesCell CountCell ProliferationDisease ProgressionEsophageal AchalasiaEsophagusHedgehog ProteinsMiceModels, BiologicalMorphogenesisMuscle, SmoothMyenteric PlexusMyocytes, Smooth MuscleNeuronsNitric OxideNitroprussidePeristalsisThe adipose tissue production of adiponectin is increased in end-stage renal disease.http://jdc.jefferson.edu/medfp/110
http://jdc.jefferson.edu/medfp/110Sun, 17 Nov 2013 17:27:42 PST
Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared with 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis factor α, interleukin 6, and high-sensitivity C-reactive protein were significantly higher in cases compared with controls. Adiponectin mRNA and protein expression in visceral and subcutaneous fat were significantly higher in cases than controls, while adiponectin receptor-1 mRNA expression was significantly increased in peripheral blood cells, muscle, and adipose tissue in cases compared with controls. Thus, our study suggests that adipose tissue production of adiponectin contributes to the high plasma levels seen in end-stage renal disease.
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Maria P Martinez Cantarin et al.AdiponectinAdipose TissueAdultAgedCardiovascular DiseasesFemaleHumansKidney Failure, ChronicMaleMiddle AgedRNA, MessengerReceptors, AdiponectinRecovery of zeta-chain expression and changes in spontaneous IL-10 production after PSA-based vaccines in patients with prostate cancer.http://jdc.jefferson.edu/medfp/109
http://jdc.jefferson.edu/medfp/109Thu, 14 Nov 2013 11:35:58 PST
Circulating T lymphocytes of patients with prostate cancer have been reported to have functional deficits, including low or absent zeta-chain expression. To determine whether these functional impairments could be reversed by prostate specific antigen-based vaccination therapy, 10 patients treated with recombinant human prostate specific antigen plus GM-CSF and eight others receiving prostate specific antigen plus oil emulsion in two pilot clinical trials were evaluated prior to and after vaccination for several immunologic end points, including zeta-chain expression and cytokine production by circulating T cells as well as the frequency of T cells able to respond to prostate specific antigen in ELISPOT assays. The flow cytometry assay for zeta-chain expression was standardized to allow for a reliable comparison of pre- vs post-vaccination samples. Prior to therapy, the patients were found to have significantly lower zeta-chain expression in circulating CD3(+) cells and a higher percentage of zeta-chain negative CD3(+) and CD4(+) cells than normal donors. The patients' peripheral blood mononuclear cells spontaneously produced more IL-10 ex vivo than those of normal controls. After vaccination, recovery of zeta-chain expression was observed in 50% of patients in both clinical trials. Also, spontaneous IL-10 secretion by peripheral blood mononuclear cells decreased following immunotherapy in patients treated with prostate specific antigen and GM-CSF. The frequency of prostate specific antigen-reactive T cells was detectable in 7 out of 18 patients vs 4 out of 18 patients prior to vaccination. Only one of 18 patients was a clinical responder. The vaccine had stimulatory effects on the patients' immune system, but post-vaccine immune recovery could not be correlated to progression-free survival in this small cohort of patients with prostate cancer.
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N Meidenbauer et al.AgedCancer VaccinesCarcinomaDisease-Free SurvivalFlow CytometryGlobinsHumansInterleukin-10MaleMiddle AgedProstate-Specific AntigenProstatic NeoplasmsT-LymphocytesTreatment OutcomeIdentification of FVIII gene mutations in patients with hemophilia A using new combinatorial sequencing by hybridization.http://jdc.jefferson.edu/medfp/108
http://jdc.jefferson.edu/medfp/108Tue, 12 Nov 2013 17:57:28 PST
BACKGROUND: Standard methods of mutation detection are time consuming in Hemophilia A (HA) rendering their application unavailable in some analysis such as prenatal diagnosis.

OBJECTIVES: To evaluate the feasibility of combinatorial sequencing-by-hybridization (cSBH) as an alternative and reliable tool for mutation detection in FVIII gene.

PATIENTS/METHODS: We have applied a new method of cSBH that uses two different colors for detection of multiple point mutations in the FVIII gene. The 26 exons encompassing the HA gene were analyzed in 7 newly diagnosed Italian patients and in 19 previously characterized individuals with FVIII deficiency.

RESULTS: Data show that, when solution-phase TAMRA and QUASAR labeled 5-mer oligonucleotide sets mixed with unlabeled target PCR templates are co-hybridized in the presence of DNA ligase to universal 6-mer oligonucleotide probe-based arrays, a number of mutations can be successfully detected. The technique was reliable also in identifying a mutant FVIII allele in an obligate heterozygote. A novel missense mutation (Leu1843Thr) in exon 16 and three novel neutral polymorphisms are presented with an updated protocol for 2-color cSBH.

CONCLUSIONS: cSBH is a reliable tool for mutation detection in FVIII gene and may represent a complementary method for the genetic screening of HA patients.

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M Chetta et al.Inhibition of effector function but not T cell activation and increase in FoxP3 expression in T cells differentiated in the presence of PP14.http://jdc.jefferson.edu/medfp/107
http://jdc.jefferson.edu/medfp/107Mon, 11 Nov 2013 08:15:57 PST
BACKGROUND: T-helper polarization of naïve T cells is determined by a complex mechanism that involves many factors, eventually leading to activation of Th1, Th2, or Th17 responses or alternatively the generation of regulatory T cells. Placental Protein 14 (PP14) is a 28 kDa glycoprotein highly secreted in early pregnancy that is able to desensitize T cell receptor (TCR) signaling and modulate T cell activation.

METHODOLOGY/PRINCIPAL FINDINGS: Prolonged antigen-specific stimulation of T cells in the presence of PP14 resulted in an impaired secretion of IFN-γ, IL-5 and IL-17 upon restimulation, although the cells proliferated and expressed activation markers. Furthermore, the generation of regulatory CD4(+)CD25(high)Foxp3(+) T cells was induced in the presence of PP14, in both antigen-specific as well as polyclonal stimulation. In accordance with previous reports, we found that the induction of FoxP3 expression by PP14 is accompanied by down regulation of the PI3K-mTOR signaling pathway.

CONCLUSIONS/SIGNIFICANCE: These data suggest that PP14 arrests T cells in a unique activated state that is not accompanied with the acquisition of effector function, together with promoting the generation of regulatory T cells. Taken together, our results may elucidate the role of PP14 in supporting immune tolerance in pregnancy by reducing T cell effector functions along with augmenting Treg differentiation.

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Zohar Ochanuna et al.AdultCell DifferentiationCells, CulturedFemaleForkhead Transcription FactorsGene ExpressionGlycoproteinsHumansLymphocyte ActivationMaleMiddle AgedPregnancy ProteinsT-LymphocytesT-Lymphocytes, Helper-InducerYoung AdultDrugs for preventing red blood cell dehydration in people with sickle cell disease.http://jdc.jefferson.edu/medfp/106
http://jdc.jefferson.edu/medfp/106Sat, 09 Nov 2013 13:30:54 PST
BACKGROUND: Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs.

OBJECTIVES: To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells.

MAIN RESULTS: Of the 51 studies identified, three met the inclusion criteria. The first study tested the effectiveness of zinc sulphate to prevent sickle cell-related crises in a total of 145 participants and showed a significant reduction in painful crises over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15). However, analysis was restricted due to limited statistical data. Changes to red cell parameters and blood counts were inconsistent. No serious adverse events were noted in the study.The second study was a Phase II dose-finding study of senicapoc (a Gardos channel blocker) compared to placebo. Compared to the placebo group the high dose senicapoc showed significant improvement in change in hemoglobin level, number and proportion of dense red blood cells, red blood cell count and indices and hematocrit. The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups. A subsequent Phase III study of senicapoc was terminated early since there was no difference observed between the treatment and control groups in the primary end point of painful crises.

AUTHORS' CONCLUSIONS: While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicenter studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.While the Phase II and the prematurely terminated phase III studies of senicapoc showed that the drug improved red cell survival (depending on dose), this did not lead to fewer painful crises.

3. How beta-agonists got a bad rap (and a black box), how a borrowed idea from the heart field was used to explore the paradoxical (beneficial) effect of beta-blockers explains paradoxical, thus paving the way for new generation of beta-adrenoceptor ligands in the treatment of asthma.

Presentation: 1 hour & 6 minutes

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Raymond B. Penn, PhDGender-sensitive reporting in medical research.http://jdc.jefferson.edu/medfp/104
http://jdc.jefferson.edu/medfp/104Sun, 03 Nov 2013 17:45:13 PST
Sex and gender differences influence the health and wellbeing of men and women. Although studies have drawn attention to observed differences between women and men across diseases, remarkably little research has been pursued to systematically investigate these underlying sex differences. Women continue to be underrepresented in clinical trials, and even in studies in which both men and women participate, systematic analysis of data to identify potential sex-based differences is lacking. Standards for reporting of clinical trials have been established to ensure provision of complete, transparent and critical information. An important step in addressing the gender imbalance would be inclusion of a gender perspective in the next Consolidated Standards of Reporting Trials (CONSORT) guideline revision. Uniform Requirements for Manuscripts Submitted to Biomedical Journals, as a set of well-recognized and widely used guidelines for authors and biomedical journals, should similarly emphasize the ethical obligation of authors to present data analyzed by gender as a matter of routine. Journal editors are also promoters of ethical research and adequate standards of reporting, and requirements for inclusion of gender analyses should be integrated into editorial policies as a matter of urgency.
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Shirin Heidari et al.Biomedical ResearchClinical Trials as TopicFemaleHumansMaleManuscripts, MedicalSex FactorsWeekly paclitaxel, gemcitabine, and external irradiation followed by randomized farnesyl transferase inhibitor R115777 for locally advanced pancreatic cancer.http://jdc.jefferson.edu/medfp/103
http://jdc.jefferson.edu/medfp/103Mon, 28 Oct 2013 17:51:57 PDT
PURPOSE: The Radiation Therapy Oncology Group (RTOG) multi-institutional Phase II study 98-12, evaluating paclitaxel and concurrent radiation (RT) for locally advanced pancreatic cancer, demonstrated a median survival of 11.3 months and a 1-year survival of 43%. The purpose of the randomized Phase II study by RTOG 0020 was to evaluate the addition of weekly low- dose gemcitabine with concurrent paclitaxel/RT and to evaluate the efficacy and safety of the farnesyl transferase inhibitor R115777 following chemoradiation.

PATIENTS AND METHODS: Patients with unresectable, nonmetastatic adenocarcinoma of the pancreas were eligible. Patients in Arm 1 received gemcitabine, 75 mg/m(2)/week, and paclitaxel, 40 mg/m(2)/week, for 6 weeks, with 50.4 Gy radiation (CXRT). Patients in Arm 2 received an identical chemoradiation regimen but then received maintenance R115777, 300 mg twice a day for 21 days every 28 days (CXRT+R115777), until disease progression or unacceptable toxicity.

RESULTS: One hundred ninety-five patients were entered into this study, and 184 were analyzable. Grade 4 nonhematologic toxicities occurred in less than 5% of CXRT patients. The most common grade 3/4 toxicity from R115777 was myelosuppression; however, grade 3/4 hepatic, metabolic, musculoskeletal, and neurologic toxicities were also reported. The median survival time was 11.5 months and 8.9 months for the CXRT and CXRT+R115777 arms, respectively.

CONCLUSIONS: The CXRT arm achieved a median survival of almost 1-year, supporting chemoradiation as an important therapeutic modality for locally advanced pancreatic cancer. Maintenance R115777 is not effective and is associated with a broad range of toxicities. These findings provide clinical evidence that inhibition of farnesylation affects many metabolic pathways, underscoring the challenge of developing an effective K-ras inhibitor.

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Tyvin A Rich et al.A review of nutritional factors in hypertension management.http://jdc.jefferson.edu/medfp/102
http://jdc.jefferson.edu/medfp/102Sun, 20 Oct 2013 18:59:02 PDT
Hypertension is a major health problem worldwide. Its attendant morbidity and mortality complications have a great impact on patient's quality of life and survival. Optimizing blood pressure control has been shown to improve overall health outcomes. In addition to pharmacological therapies, nonpharmacological approach such as dietary modification plays an important role in controlling blood pressure. Many dietary components such as sodium, potassium, calcium, and magnesium have been studied substantially in the past decades. While some of these nutrients have clear evidence for their recommendation, some remain controversial and are still of ongoing study. Dietary modification is often discussed with patients and can provide a great benefit in blood pressure regulation. As such, reviewing the current evidence will be very useful in guiding patients and their physician and/or dietician in decision making. In this review article of nutritional factors in hypertension management, we aim to examine the role of nutritional factors individually and as components of whole dietary patterns.
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Ha Nguyen et al.